Amygdala

Anatomy

• An almond-shaped nuclear complex in the medial temporal lobe, in front of the hippocampal head, within the uncus.
• Three main groups and a division of labor: Basolateral complex (lateral, basal, accessory basal): the gateway for sensory input and the site of learning. Central nucleus: the main output. Medial and cortical nuclei: olfactory and social-reproductive signals. B
• Intercalated cells mediate inhibition via the vmPFC. The bed nucleus of the stria terminalis (BNST) is the “extended amygdala”.
• Blood supply: anterior choroidal artery, MCA branches.
• The outputs are a map of symptoms. Central nucleus → hypothalamus and BNST (HPA axis, cortisol), PAG (freezing), locus coeruleus (arousal), parabrachial and vagal nuclei (heart rate, breathing). The bodily symptoms of anxiety can be read from these outputs. B
• Two input routes: a fast, coarse route from the thalamus and a slow, detailed route from the cortex (LeDoux’s “low and high road”). The importance of the fast route in humans is debated; in teaching it should be presented as a model. B

Functions

• Threat detection and Pavlovian fear conditioning.
• Emotional salience: attention to negative and positive stimuli.
• Rapid processing of facial expressions (especially fear) and the eye region.
• Strengthening of emotional memories (modulation of the hippocampus).
• Initiation of the autonomic and endocrine stress response (hypothalamus–HPA).
• Social evaluation: trustworthiness, personal space.
• Reward value: learns and updates stimulus–value associations; the basolateral amygdala → nucleus accumbens pathway guides motivated behavior. The amygdala is not only a fear center (Baxter and Murray, 2002). B
• Feeling fear of external threats depends on the amygdala: S.M., with bilateral amygdala damage, felt no fear of snakes, spiders or a haunted house (Feinstein et al., 2011). B
• But the amygdala is not needed for internal threat: the same patients experienced fear and panic attacks after inhaling 35% CO₂ (Feinstein et al., 2013). An important finding showing the role of interoceptive pathways (brainstem, insula) in panic disorder. B
• Uncertainty and unpredictability: when it is unknown when a threat will come, the response shifts to the BNST. A distinction is made between phasic fear (amygdala) and sustained anxiety (BNST). B

Connections and chemistry

• vmPFC / mPFC (regulation)
• Hypothalamus (HPA axis, CRH)
• PAG and brainstem (defense, autonomic)
• Hippocampus
• Nucleus accumbens
• Locus coeruleus (noradrenaline), serotonin, GABA–benzodiazepine receptors
• Salience network: together with the dorsal ACC and anterior insula
• Uncinate fasciculus: OFC and temporal pole
• Stria terminalis: BNST and hypothalamus; ventral amygdalofugal pathway: hypothalamus and mediodorsal thalamus
• CRF: drives the stress response in the central nucleus
• Oxytocin: reduces the amygdala response; a single dose of intranasal oxytocin lowered activation to fear stimuli (Kirsch et al., 2005, adult men) C
• Endocannabinoid (CB1): required for fear extinction (Marsicano et al., 2002, mice) B

Development

Developmental course through childhood and adolescence.

• Develops early; in infancy the caregiver’s presence buffers the amygdala response.
• In adolescence, amygdala reactivity to emotional faces increases while mPFC regulation is not yet mature.
• Institutional care: later adoption was associated with larger amygdala volume, weaker emotion regulation and more anxiety (Tottenham et al., 2010). In children who experienced deprivation, negative amygdala–mPFC connectivity appears early; this “accelerated maturation” is interpreted as a stress adaptation (Gee et al., 2013, PNAS). B
• The sign switch of amygdala–mPFC connectivity: positive (immature) before age 10, negative (regulatory) after age 10. Amygdala reactivity declines at the same time (Gee et al., 2013, J Neurosci; ages 4–22). B
• Parental buffering: a photo of the mother suppresses the amygdala response in children and brings connectivity closer to the mature pattern; the effect is absent in adolescents. Childhood may be a sensitive period for this circuit (Gee et al., 2014). B
• Subcortical gray matter volume reaches its lifetime peak at about age 14.4 (Bethlehem et al., 2022; 123,984 MRI scans). A

Clinical

• Anxiety disorders: a child and adolescent fMRI meta-analysis (48 studies, more than 2,000 participants) found bilateral amygdala hyperactivation in internalizing disorders, especially anxiety (Ashworth et al., 2021). A In adolescent GAD, the right amygdala response to unconscious (masked) angry faces is increased and relates to severity, without a compensatory increase in vlPFC (Monk et al., 2008). B
• Conduct disorder + CU traits: reduced amygdala response to fearful faces. In reactive aggression, by contrast, the response is increased.
• ASD: large amygdala in boys aged 7–12, with the difference disappearing in adolescence (Schumann et al., 2004). In a large lifespan sample (ENIGMA-ASD) the amygdala is slightly smaller on average (d ≈ 0.11–0.16) (van Rooij et al., 2018). The difference depends on age; the generalization “the amygdala is enlarged in ASD” should be avoided. A/B
• Depression and PTSD: amygdala hyperreactivity; impaired fear extinction in PTSD (together with the vmPFC). B
• ADHD: ENIGMA (1,713 patients, 1,529 controls) found smaller amygdala volume in ADHD; the difference is marked in children and disappears in adults (Hoogman et al., 2017). The effect is small and not diagnostic. A
• Conduct disorder: ENIGMA-Antisocial Behavior: smaller amygdala volume (d ≈ 0.13); differences are more widespread in those with high callous-unemotional (CU) traits (Gao et al., 2024). A
• Williams syndrome (7q11.23 microdeletion): reduced amygdala response to angry or fearful faces (social fearlessness) but increased response to nonsocial threat scenes (nonsocial anxiety). The same structure works in opposite directions depending on the type of stimulus (Meyer-Lindenberg et al., 2005). B

Treatment

This region from the perspective of medication, psychotherapy and neuromodulation. Letter badges are evidence levels.

• Pediatric GAD: those with a higher amygdala response before treatment responded better to fluoxetine or CBT; effective treatment reduces amygdala hyperactivity (McClure et al., 2007). C
• Benzodiazepines: act via the dense GABA-A receptors in the amygdala. Short-term and cautious use in children.
• Neurofeedback: 6 sessions of training with an fMRI-derived EEG signature (the “amygdala electrical fingerprint”) reduced alexithymia and improved stress coping in 180 healthy adults undergoing stressful military training (Keynan et al., 2019). Cheap and portable; adolescent studies are ongoing. C
• Deep brain stimulation: basolateral amygdala stimulation in refractory combat PTSD (Langevin et al., 2016). Adults only, experimental. C

Assessment

Neuropsychological tasks and measures that probe this region's function.

• Fear conditioning and extinction paradigms
• Emotional face recognition (NEPSY-II Affect Recognition)
• Attention bias (dot-probe), startle reflex
• Reading the Mind in the Eyes Test (child version): the amygdala and temporal network in social cognition.

Lesions and damage

Clinical findings expected with damage or dysfunction.

• Urbach-Wiethe disease (the case of S.M.): no fear of external threats, no sense of personal space; but panic with CO₂ (Feinstein 2011, 2013).
• Klüver-Bucy syndrome (bilateral anterior temporal): hyperorality, hypersexuality, fearlessness, visual agnosia.
• Mesial temporal lobe epilepsy: amygdala-origin aura (rising epigastric sensation, sudden fear). In children it can be confused with a panic attack.

In the model

How this structure is defined in the 3D model, and the data source.

CerebrA amygdala label.

References

Full citations for the card; links go to the paper (DOI) or a PubMed search.

1. Ashworth E, Brooks SJ, Schiöth HB. Neural activation of anxiety and depression in children and young people: a systematic meta-analysis of fMRI studies. Psychiatry Res Neuroimaging 2021;311:111272. Search PubMed
2. Bethlehem RAI et al. Brain charts for the human lifespan. Nature 2022. Search PubMed
3. Feinstein JS et al. The human amygdala and the induction and experience of fear. Curr Biol 2011. Search PubMed
4. Feinstein JS et al. Fear and panic in humans with bilateral amygdala damage. Nat Neurosci 2013. Search PubMed
5. Gao Y, Staginnus M and ENIGMA-Antisocial Behavior WG. Cortical structure and subcortical volumes in conduct disorder. Lancet Psychiatry 2024;11(8):620–632. Search PubMed
6. Gee DG et al. A developmental shift from positive to negative connectivity in human amygdala–prefrontal circuitry. J Neurosci 2013. Search PubMed
7. Gee DG et al. Early developmental emergence of human amygdala–prefrontal connectivity after maternal deprivation. PNAS 2013. Search PubMed
8. Gee DG et al. Maternal buffering of human amygdala-prefrontal circuitry during childhood but not during adolescence. Psychol Sci 2014;25(11). Search PubMed
9. Hoogman M et al. Subcortical brain volume differences in participants with ADHD. Lancet Psychiatry 2017;4(4). Search PubMed
10. Keynan JN et al. Electrical fingerprint of the amygdala guides neurofeedback training for stress resilience. Nat Hum Behav 2019;3:63–73. Search PubMed
11. Kirsch P et al. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 2005. Search PubMed
12. Langevin JP et al. Deep brain stimulation of the basolateral amygdala for treatment-refractory PTSD. Biol Psychiatry 2016. Search PubMed
13. McClure EB et al. fMRI predictors of treatment outcome in pediatric anxiety disorders. Psychopharmacology 2007;191(1):97–105. Search PubMed
14. Monk CS et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 2008. Search PubMed
15. Schumann CM et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci 2004. Search PubMed
16. Tottenham N et al. Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Dev Sci 2010;13(1):46–61. Search PubMed
17. van Rooij D et al. Cortical and subcortical brain morphometry differences between patients with ASD and healthy individuals across the lifespan (ENIGMA-ASD). Am J Psychiatry 2018;175(4):359–369. Search PubMed
18. Marsicano G et al. The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002;418:530–534. Search PubMed
19. Meyer-Lindenberg A et al. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci 2005. Search PubMed
20. Klasik (yerleşik, ayrıca aranmadı): Baxter MG, Murray EA. The amygdala and reward. Nat Rev Neurosci 2002; LeDoux JE, korku devresi. Search PubMed